1. Field of the Invention
The present invention relates to a differentiation inducer to brown-like adipocytes of white adipocytes, the differentiation inducer which contains a reaction product of hydroxystilbenes and sinapic acid obtained by a synthesis method which is a very simple method and is applicable also to foods.
2. Description of the Background Art
Adipocytes constituting the adipose tissue of mammals include two kinds of adipocytes, white adipocytes and brown adipocytes. The white adipocytes mainly have a role of accumulating the chemical energy taken in the form of triglyceride. On the other hand, the brown adipocytes have a role of converting the accumulated energy to heat. The brown adipocytes generate from myoblasts and are colored brown due to a large number of mitochondria contained in the cells. The brown adipocytes generate heat by the action of Uncoupling protein 1 (UCP1) expressed in the mitochondria (Non-patent Literature 1).
A large amount of the brown adipose tissue constituted by the brown adipocytes can be seen in human infant, but the presence of brown fat in the tissue decreases with growth. It has been considered that since the derived stem cells are different, the brown adipocytes are not expressed from the white adipocytes. In recent years, however, the existence of “brown-like adipocytes” which show the same response as that of the brown adipocytes in the white adipose tissue has been clarified (Non-patent Literature 2). Although the brown-like adipocytes are derived from the white adipocytes, the amount of mitochondria in the brown-like adipocytes is markedly large as compared with that of the white adipocytes and the accumulated lipid energy is efficiently converted to heat energy. Therefore, the differentiation induction of the white adipocytes to the brown-like adipocytes has drawn attention as a fundamental medical treatment method of obesity or diabetes.
However, it is difficult to induce the differentiation of the white adipocytes to the brown-like adipocytes. Confirmed methods are only prolonged cold stimulation, stimulus by adrenalin (Non-Patent Literature 1), addition of peroxisome proliferator-activated receptor (PPARγ) agonist (Non-Patent Literature 3), and the like. In addition, in all the methods above, the differentiation induction effect is limited only in subcutaneous adipocytes. These methods do not have an effect to the mouse-derived preadipocyte 3T3-L1 as the model cell of the white adipocytes and the visceral adipose which is the cause of the metabolic syndrome typified by obesity and diabetes. Moreover, although a compound having an expression amplification effect of the UCP1 gene to the human visceral adipocytes has been reported in Patent Literature 1, the working concentration is very high, so that it is difficult to achieve the effective concentration in the living body and bronzing of the white adipocytes is not referred to.
On the other hand, it is supposed that the useful physiological effect of red wine referred to as so-called “French paradox” is caused by various kinds of bioactive functions including the anti-oxidization ability of resveratrol. The resveratrol is one of the hydroxystilbenes mostly contained in grape pericarp and peanut red bark. The resveratrol is known to be a plant-derived compound having a calorie restriction effect through sirtuin and various activities, such as an antifungal effect, an antibacterial effect, and an anti-inflammation effect (Non-Patent Literature 4). Furthermore, it has been reported that the resveratrol has action of differentiation to adipocytes through the expression promotion of sirtuin and suppression of the accumulation of fat (Non-Patent Literature 5). However, under the circumstances where there arises a doubt as a result of an experiment to Macacus rhesus as to where the calorie restriction itself has an effect useful for life extension (Non-Patent Literature 6), the calorie restriction effect through sirtuin to human beings of the resveratrol is not also certain. Moreover, although it has been reported that the resveratrol has a gene expression enhancement effect of Uncoupling protein UCP2 specifically expressed in the white adipocytes (Patent Literature 2), the differentiation effect from the white adipocytes to the brown-like adipocytes of the resveratrol has not been referred to at all so far.
The sinapic acid is known to be one of secondary metabolites of plants, a component mostly present in the plant kingdom as precursors of lignin and lignan as the main component of trees, and mostly contained in fruits, such as apples, grains, such as wheat, and the cruciferous plant, such as broccoli sprout. An anti-oxidization effect of the sinapic acid and derivatives thereof is known but an effect of differentiation to the brown-like adipocytes from the white adipocytes thereof is not known at all.
Thus, a development of fundamental medical treatment and prevention agents which prevent and medically treat the metabolic syndrome, not by suppression of appetite or suppression of fat absorption, but by changing the properties of the adipocytes themselves to change metabolism and functional foods containing the agents has been desired until today. However, a substance which is admitted to have a sufficient effect to all the white adipocytes has not been found so far, and an early development thereof has been desired.